This invention relates to a process for preparing finely divided micro-particles of tyrosine having a water-soluble glutaraldehyde-treated ragweed pollen extract as allergen dispersed therein for use in desensitisation therapy of persons who are liable to allergic reactions and the product thereof.
U.S. Pat. No. 3,792,159 describes a process for preparing injectable compositions for use in desensitisation therapy which consist of finely-divided micro-particles of tyrosine having an allergen dispersed therein, which process comprises mixing a solution of tyrosine in a strong aqueous acid with an aqueous or water-miscible solution of the desired allergen and simultaneously or subsequently neutralising the resultant solution whereby finely-divided micro-particles of tyrosine containing the allergen are precipitated; and subsequently separating the said micro-particles. The Patent refers quite generally to allergens and relates to a valuable method of preparing tyrosine micro-particles containing such allergens. The process conditions are such that the process is effective only with water-soluble allergens and several examples of such allergens are described.
U.S. Pat. No. 3,541,201 describes the preparation of finely divided micro-particles of tyrosine having allergens dispersed therein. It is believed clear from this Patent that the allergens must be water soluble.
U.S. Pat. No. 3,794,630 and its divisional U.S. Pat. No. 3,761,585 describe the preparation and use for desensitization therapy of a particular class of allergens not mentioned or suggested in the aforesaid U.S. Pat. Nos. 3,792,159 and 3,541,201, namely allergens that have been modified by treatment inter alia with glutaraldehyde. These modified allergens probably contain intra-molecular cross-linking with possibly some inter-molecular cross-linking and have reduced allergenicity relative to the unmodified allergen. In order to obtain a modified product of the desired utility it is recommended in U.S. Pat. Nos. 3,794,630 and 3,761,585 that the modification process is carried out under conditions which yield a water-insoluble or sparingly water-soluble modified allergen, and only modified allergens of such solubility are specifically described. For injection, it is disclosed in these Patents that the modified allergens can be formulated with adjuvants such as tyrosine, and examples of such formulation with water-insoluble and sparingly water-soluble modified allergens are given.
It is believed that the skilled reader of U.S. Pat. Nos. 3,794,630 and 3,761,585 attempting to prepare a product having the desired utility disclosed therein would follow the recommendations in the Patents and would adjust the modification process to give water-insoluble or sparingly water-soluble modified allergens. It is similarly believed that any formulation with adjuvants would be carried out with modified allergens of this solubility. As would therefore be expected, there is no specific disclosure in the Patents of the preparation of a water soluble modified allergen, nor is there any disclosure or recommendation in the Patents of the formulation of a water-soluble modified allergen with an adjuvant. It is further believed that the skilled reader of U.S. Pat. Nos. 3,792,159 and 3,541,201 would not consider using the modified allergens of U.S. Pat. Nos. 3,794,630 and 3,761,585 in the process and formulations described therein, as for such use the modified allergens would have to be water soluble while the modified allergens recommended in U.S. Pat. Nos. 3,794,630 and 3,761,585 as having the desired utility are water insoluble or sparingly water-soluble. Adjustment of the modification process described in U.S. Pat. Nos. 3,794,630 and 3,761,585 to give water soluble modified allergens would be going directly against the teaching therein, and would result in a product for which no utility predictions could be made from these Patents.
It has now surprisingly been discovered that water soluble glutaraldehyde modified ragweed pollen extract may be used in the process of U.S. Pat. No. 3,792,159 to give a product which advantageously combines efficacy with safety in desensitization therapy.